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Astragaloside IV Attenuates Glutamate-Induced Neurotoxicity in PC12 Cells through Raf-MEK-ERK Pathway
- Source :
- PLoS ONE, Vol 10, Iss 5, p e0126603 (2015), PLoS ONE
- Publication Year :
- 2015
- Publisher :
- Public Library of Science (PLoS), 2015.
-
Abstract
- Astragaloside IV (AGS-IV) is a main active ingredient of Astragalus membranaceus Bunge, a medicinal herb prescribed as an immunostimulant, hepatoprotective, antiperspirant, a diuretic or a tonic as documented in Chinese Materia Medica. In the present study, we employed a high-throughput comparative proteomic approach based on 2D-nano-LC-MS/MS to investigate the possible mechanism of action involved in the neuroprotective effect of AGS-IV against glutamate-induced neurotoxicity in PC12 cells. Differential proteins were identified, among which 13 proteins survived the stringent filter criteria and were further included for functional discussion. Two proteins (vimentin and Gap43) were randomly selected, and their expression levels were further confirmed by western blots analysis. The results matched well with those of proteomics. Furthermore, network analysis of protein-protein interactions (PPI) and pathways enrichment with AGS-IV associated proteins were carried out to illustrate its underlying molecular mechanism. Proteins associated with signal transduction, immune system, signaling molecules and interaction, and energy metabolism play important roles in neuroprotective effect of AGS-IV and Raf-MEK-ERK pathway was involved in the neuroprotective effect of AGS-IV against glutamate-induced neurotoxicity in PC12 cells. This study demonstrates that comparative proteomics based on shotgun approach is a valuable tool for molecular mechanism studies, since it allows the simultaneously evaluate the global proteins alterations.
- Subjects :
- Cell signaling
Cellular differentiation
Glutamic Acid
lcsh:Medicine
Pharmacology
Biology
Proteomics
Neuroprotection
PC12 Cells
Protein Interaction Mapping
medicine
Animals
Extracellular Signal-Regulated MAP Kinases
lcsh:Science
Neurons
Principal Component Analysis
Multidisciplinary
Gene Expression Profiling
lcsh:R
Neurotoxicity
Cell Differentiation
Molecular Sequence Annotation
Saponins
medicine.disease
MAP Kinase Kinase Kinases
Triterpenes
High-Throughput Screening Assays
Rats
Blot
Neuroprotective Agents
Mechanism of action
Biochemistry
Gene Expression Regulation
raf Kinases
lcsh:Q
medicine.symptom
Signal transduction
Research Article
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 10
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....3eb300b92d21d264b13d255a3469913e